Osteomyelitis, as a severe bone disease caused by bacterial infection, can result in lifelong disability or fatal sepsis. Considering that the infection is stubborn and deep-sited in bone tissue, in situ and rapid treatments for osteomyelitis remain a significant challenge. Herein, we prepare an ultrasound (US)-activated single-atom catalyst that consists of a Au nanorod (NRs)-actuated single-atom-doped porphyrin metal− organic framework (HNTM-Pt@Au) and red cell membrane (RBC), which can efficiently treat methicillin-resistant Staphylococcus aureus (MRSA)-infected osteomyelitis under US. Besides the outstanding performance in the field of photocatalysis, we find that single atoms (such as Pt, Au, Cu) also improve the sonocatalytic ability of the sonosensitizer. Due to the strong electron-trapping and oxygen adsorption capacity, the Pt single atom endows RBC-HNTM-Pt@Au with an excellent sonocatalytic activity. It shows an excellent antibacterial performance with an antibacterial efficiency of 99.9% toward MRSA under 15 min of US irradiation. Meanwhile, the RBC-HNTM-Pt@Au can be propelled directionally under US and thus dynamically neutralize the secreted toxins. The MRSA-infected osteomyelitis in rat tibia was successfully treated, which shows negligible bone loss, reduced inflammation response, and great biocompatibility. This work presents an efficient sonodynamic therapy for the treatment of deep tissue infections via a multifunctional single-atom catalyst.

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Since the last IAEA Fusion Energy Conference in 2018, significant progress of the experimental program of HL-2A has been achieved on developing advanced plasma physics, edge localized mode (ELM) control physics and technology. Optimization of plasma confinement has been performed. In particular, high-N H-mode plasmas exhibiting an internal transport barrier have been obtained (normalized plasma pressure N reached up to 3). Injection of impurity improved the plasma confinement. ELM control using resonance magnetic perturbation (RMP) or impurity injection has been achieved in a wide parameter regime, including Types I and III. In addition, the impurity seeding with supersonic molecular beam injection (SMBI) or laser blow-off (LBO) techniques has been successfully applied to actively control the plasma confinement and instabilities, as well as the plasma disruption with the aid of disruption prediction. Disruption prediction algorithms based on deep learning are developed. A prediction accuracy of 96.8% can be reached by assembling convolutional neural network (CNN). Furthermore, transport resulted from a wide variety of phenomena such as energetic particles and magnetic islands have been investigated. In parallel with the HL-2A experiments, the HL-2M mega-ampere class tokamak was commissioned in 2020 with its first plasma. Key features and capabilities of HL-2M are briefly presented.

Background Although the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM) with or without heart failure (HF), the impact of SGLT2i on cardiac remodelling remains to be established. Methods We searched the PubMed, Embase, Cochrane Library and Web of Science databases up to November 16th, 2020, for randomized controlled trials reporting the effects of SGLT2i on parameters of cardiac structure, cardiac function, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level or the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in T2DM patients with or without chronic HF. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed based on the stage A–B or stage C HF population and HF types. Results Compared to placebo or other antidiabetic drugs, SGLT2i showed no significant effects on left ventricular mass index, left ventricular end diastolic volume index, left ventricular end systolic volume index, or left atrial volume index. SGLT2i improved left ventricular ejection fraction only in the subgroup of HF patients with reduced ejection fraction (MD 3.16%, 95% CI 0.11 to 6.22, p = 0.04; I2 = 0%), and did not affect the global longitudinal strain in the overall analysis including stage A–B HF patients. SGLT2i showed benefits in the E/e’ ratio (MD − 0.45, 95% CI − 0.88 to − 0.03, p = 0.04; I2 = 0%), plasma NT-proBNP level (SMD − 0.09, 95% CI − 0.16 to − 0.03, p = 0.004; I2 = 0%), and the KCCQ score (SMD 3.12, 95% CI 0.76 to 5.47, p  = 0.01; I2 = 0%) in the overall population. Conclusion The use of SGLT2i was associated with significant improvements in cardiac diastolic function, plasma NT-proBNP level, and the KCCQ score in T2DM patients with or without chronic HF, but did not significantly affect cardiac structural parameters indexed by body surface area. The LVEF level was improved only in HF patients with reduced ejection fraction.

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therapy (PDT), the low tissue penetration of light remains a fatal weakness. [1][2][3][4] Relatively, ultrasound (US) with a high tissue-penetration depth has become an important diagnostic tool in clinics. [5] High-intensity focused US can ablate cancer cells in clinical applications through instantaneous heating (65-100°C). [6] Whereas, HIFU cannot eliminate bacteria efficiently under above temperature in a short time without tissue scald. [7] For the SDT, it is desirable to develop a highly efficient sonosensitizer to kill pathogens under mild US (medical imaging grade).At present, the reported sonosensitizer are mainly divided into organic and inorganic categories. [8] Inorganic sonosensitizers, such as TiO 2 NPs, ZnO, Fe 3 O 4 , MnWO x , BaTiO 3, and black phosphorus can generate ROS under US irradiation, but most of them are needed to be decorated with noble metals to improve their SDT efficiency. [9][10][11][12][13][14] In addition, most inorganic nanomaterials cannot be biodegraded, which leads to long-term body retention. [15] Currently, the most widely used organic sonosensitizers in SDT are porphyrins and their derivatives. [16,17] Although most organic sonosensitizers have good biocompatibility, biodegradability, and high ROS production efficiency under US irradiation. [18,19] Sonodynamic therapy (SDT) with non-invasiveness and high tissue-penetrating ability has attracted widespread interest in treating deep-seated tumors or infections. To enhance the treatment efficacy of SDT, the development of high-efficiency and stable sonosensitizers are still needed. Herein, a defective homojunction porphyrin-based metal-organic framework (MOF) with greatly enhanced sonocatalytic ability is easily prepared and used for SDT of osteomyelitis infected by methicillin-resistant Staphylococcus aureus (MRSA). Acetic acid and benzoic acid are chosen as modulators during the hydrothermal synthesis of porphyrin-based MOF. It is found that the crystal structure of MOF shifts from PCN-222 to PCN-224 as the amount of acetic acid increases. Interestingly, the defective PCN (D-PCN) contains a two-phase homojunction structure of PCN-222/PCN-224. The sonocatalytic reactive oxygen species production presents a volcano-type trend with increased acetic acid, among which D-PCN-2 with more content of PCN-224 has the best sonocatalytic antibacterial ability. The reduced band gap introduced a defect, and type-II homojunction structures of D-PCN-2 improve the separation of the ultrasound-triggered electron hole, which significantly enhances the SDT effect. Through a mixed linker approach, this work develops a new defect-induced homojunction MOF with great performance for SDT of MRSA-infected osteomyelitis.

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